Leukotrienes are a family of endogenous metabolites of arachidonic acid which play an integral role in regulating inflammatory events. Since their discovery in the late seventies, many have worked to determine the biosynthesis of leukotrienes with an eye toward mediating inflammatory responses. Much of this work has focused on the enzymes used in the conversion of arachidonic acid to leukotrienes and prostaglandins, namely 5-lipoxygenase (5-LO) and cyclooxygenase (CO). The present invention relates to substituted pyrazole derivatives, and more particularly, to 1,5-diphenyl-1-propyn-3-ylpyrazoles. These compounds inhibit the production of the arachidonic acid products associated with 5-lipoxygenase and cyclooxygenase, namely, 5-HETE and PgD.sub.2 respectively. These compounds inhibit the production of 5-HETE and PgD.sub.2 at doses equal to or below other pharmacologically active 5-LO and CO inhibitors. In addition to the aforementioned in vitro screens, particular compounds of the invention inhibit the production of leukotriene B.sub.4 (LTB.sub.4), a 5-LO product and prostaglandin (TXB.sub.2), a CO product in an animal model. Therefore, compounds of the invention are potentially useful in alleviating inflammatory diseases associated with these products such as asthma, arthritis, hypersensitivity, myocardial ischemia, dermatological conditions such as psoriasis and dermatitis, and gastrointestinal inflammatory conditions, such as, inflammatory bowel syndrome in mammals. The compounds may also be employed to treat or suppress the signs or symptoms of adult respiratory distress syndrome. Although some compounds of the invention effectively inhibit on the products of either 5-LO or CO, there are some compounds which inhibit both enzymes. These dual inhibitors are believed to be useful in treating both acute and chronic stages of inflammatory disease states.
Although there are other agents which inhibit 5-LO and CO, due to the therapeutic utility of these compounds, further compounds having this utility are desired.